UMMS Affiliation
Department of Neurobiology; Freeman Lab; Graduate School of Biomedical Sciences, Neuroscience Program
Publication Date
2014-11-04
Document Type
Article
Disciplines
Molecular and Cellular Neuroscience | Neuroscience and Neurobiology
Abstract
Glial cells are exquisitely sensitive to neuronal injury but mechanisms by which glia establish competence to respond to injury, continuously gauge neuronal health, and rapidly activate reactive responses remain poorly defined. Here, we show glial PI3K signaling in the uninjured brain regulates baseline levels of Draper, a receptor essential for Drosophila glia to sense and respond to axonal injury. After injury, Draper levels are up-regulated through a Stat92E-modulated, injury-responsive enhancer element within the draper gene. Surprisingly, canonical JAK/STAT signaling does not regulate draper expression. Rather, we find injury-induced draper activation is downstream of the Draper/Src42a/Shark/Rac1 engulfment signaling pathway. Thus, PI3K signaling and Stat92E are critical in vivo regulators of glial responsiveness to axonal injury. We provide evidence for a positive auto-regulatory mechanism whereby signaling through the injury-responsive Draper receptor leads to Stat92E-dependent, transcriptional activation of the draper gene. We propose that Drosophila glia use this auto-regulatory loop as a mechanism to adjust their reactive state following injury.
Rights and Permissions
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
10.1371/journal.pbio.1001985
Source
PLoS Biol. 2014 Nov 4;12(11):e1001985. doi: 10.1371/journal.pbio.1001985. eCollection 2014. Link to article on publisher's site
Journal/Book/Conference Title
PLoS biology
Related Resources
PubMed ID
25369313
Repository Citation
Doherty JE, Sheehan AE, Bradshaw R, Fox AN, Lu T, Freeman MR. (2014). PI3K signaling and Stat92E converge to modulate glial responsiveness to axonal injury. Open Access Articles. https://doi.org/10.1371/journal.pbio.1001985. Retrieved from https://escholarship.umassmed.edu/oapubs/2456
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
First author Johnna Doherty is a doctoral student in the Neuroscience Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.